In Vivo Voltammetric Detection of Rat Brain Lactate with Carbon Fiber Microelectrodes Coated with Lactate Oxidase Nataliya F. Shram,* ,†,‡ Larissa I. Netchiporouk, ‡,§ Claude Martelet, † Nicole Jaffrezic-Renault, † Chantal Bonnet, § and Raymond Cespuglio § Laboratory of Physicochemistry of Interfaces, UMR CNRS 5621 IFoS, Ecole Centrale de Lyon, BP 163, 69131 Ecully Cedex, France, Sector of Bioelectronics, Kiev University, P.O. Box 152, Kiev-1, 252001, Ukraine, and Department of Experimental Medicine, U INSERM 480, Claude Bernard University, 8 avenue Rockefeller, 69373 Lyon Cedex, France To allow rat brain lactate measurement in vivo, a specific sensor based on a carbon fiber (O) 30 μm) microelec- trode coated with lactate oxidase was prepared. Com- bined with the differential normal pulse voltammetry measurement method, such a sensor, with a sensitivity of 9.15 ( 0.91 mA‚M -1 ‚cm -2 , provided a lactate linear response in concentrations ranging from 0 .1 to 2 .0 mM. The measurements performed appeared to be essentially insensitive to usual interference caused by the electro- active compounds present in the brain (ascorbic acid and peptides). In vivo detection performed in the cortex of the anesthetized rat led to the determination of a lactate concentration of 0 .4 1 ( 0.02 mM. Moreover, to validate the results obtained in vivo, an ex vivo determination of the lactate level was also performed in samples of brain tissue, plasma, and cerebrospinal fluid, using both vol- tammetry and a clinical analyzer with colorimetric-based detection. A good correlation was observed between the sets of data established by both methods. Direct in vivo measurements of lactate either in tissue or in biological fluids such as cerebrospinal fluid (CSF) or plasma are of great interest for studies related to energy production in anaerobic conditions. 1 It is also reported that alterations in the processes of production and delivery of this compound may contribute to damage of the central nervous system in some pathological situations, such as hypoxia, ischemia, trauma, and seizures. 2,3 Presently, reports on lactate sensors are relatively rare; this is particularly true for those dealing with direct in vivo detection. 4-7 Regarding the sensors proposed, there are some general requirementssspecificity, stability, lack of interferences, and low cost. Besides the above aspects, in vivo application also implies some additional restrictions concerning the electrode material and configuration. In this sense, carbon fiber is now reported to be one of the most convenient materials due to its high biocompatibility and micrometric dimensions (8-30 μm). The suitability of such material is also reinforced by the possibility to improve the sensitivity of the measurements by chemical or electrochemical treatment of its surface. 8-14 Concerning the measuring method, amperometry with con- stant potential remains the most commonly used, 4,6,7,15-20 despite its drawbacks: insufficient specificity toward the substrate of interest, since the electroactive species with a lower oxidation potential can contribute to the sensor response, and electrode fouling by high molecular components in the physiological medium. From this point of view, differential normal pulse * Address correspondence to this author, currently at Claude Bernard University. Phone: 33-4-78 77 71 26. Fax: 33-4-78 77 71 72. 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